{"doi":"10.1111/jnc.15894","title":"Emerging_Group_Leaders_Symposia","abstract":"Apolipoprotein E (apoE) is best known for its lipid transport capacity in the brain but also for its association with healthy aging and agerelated neuronal disorders including Alzheimer's disease (AD).While most research has concentrated on the pathologies associated with apolipoprotein E allelic variations, the mechanisms of action of apoE and its neurochemical effect in the brain remain poorly understood.In a series of clinical studies, we showed that individuals with the high-risk variant of apoE have increased ferritin in their brain, and we also showed that elevated ferritin (the major iron storage protein) was associated with accelerated cognitive decline in individuals at risk of AD.Here, we present data supporting a new function of apoE in protecting neurons from a cell death pathway termed ferroptosis.Ferroptosis is a cell death pathway characterized by the accumulation of lethal lipid hydroperoxides resulting from iron-dependent oxidation of polyunsaturated fatty acids.We demonstrate that apoE inhibits ferroptosis via activation of the PI3K/AKT signaling pathway and subsequent inhibition of the autophagic degradation of ferritin (ferritinophagy), thus preventing iron release and ferroptosis.We further identified an association between genetic variants of apoE receptors and slower cognitive decline in clinical cohorts of AD.In preliminary work, we show that one apoE receptor variant was associated with an increased protection from ferroptosis in an apoEdependent process.However, the underlying mechanisms are still unknown.These data support ferroptosis as a mechanism of neurodegeneration in AD and provide new insight into the role of apoE and apoE receptors in the pathology of AD, which may help develop new diagnostic and therapeutic approaches towards the disease.","journal":"Journal of Neurochemistry","year":2023,"id":410117,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9603,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T01:21:31.144858Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}